Unusual, selective, reductive, deoxygenation of cyclopentenone alcohols

Article abstract of DOI:10.1016/j.tetlet.2014.07.122

A selective, reductive, deoxygenation of 2-aryl-4-hydroxycyclopent-2-en-1-ones to afford 2-aryl-cyclopent-2-en-1-ones was achieved by NaBH₄-CeCl₃in methanol.

Full text of DOI:10.1016/j.tetlet.2014.07.122

Tetrahedron Letters 55 (2014) 5241–5243
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Tetrahedron Letters
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Unusual, selective, reductive, deoxygenation of cyclopentenone
alcohols
⇑
Suhas R. Bavikar, Trupti P. Lasonkar, Subhash P. Chavan, Hanumant B. Borate
Division of Organic Chemistry, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411 008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A selective, reductive, deoxygenation of 2-aryl-4-hydroxycyclopent-2-en-1-ones to afford 2-aryl-cyclo-
pent-2-en-1-ones was achieved by NaBH4–CeCl3 in methanol.
Received 26 May 2014
Revised 30 July 2014
Accepted 31 July 2014
Available online 12 August 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopentenone alcohol
Luche reduction
Reductive deoxygenation
Enone
OMe
OMe
Reduction of conjugated ketone functionality with sodium
borohydride in methanol in the presence of rare earth halides to
afford allylic alcohols was reported by Jean-Louis Luche in 1978.1
Gemal and Luche further reported selective reduction of ketone
in the presence of aldehyde using cerium chloride.2 Various aspects
of this reaction were studied extensively3–12 by Luche and subse-
quently by many other chemists to explore the utility of this reac-
tion. It has been found that during this reaction the carbonyl
functionality is reduced to alcohol in a stereoselective manner
making the method useful in the synthesis of optically active alco-
hols. This reaction has continued to attract synthetic chemists and
recently it has been reported by Zhang and co-workers13 that it can
O
O
OMe
OMe
CHO
OMe
OMe
OMe
CH2OH
OMe
CeCl3, NaBH4,
MeOH
HO
45%
1a
2a
Scheme 2. Reduction of substituted cyclopentenone alcohol 1a.
OCH3
OCH3
OCH3
be utilized for deoxygenation of
a,b-unsaturated acylphenols to
O
O
OCH3
obtain 2-allylphenols as depicted in Scheme 1. In the same publi-
cation, it has been reported that 2-acylphenols can also be con-
verted to 2-ethylphenols using the same strategy.
During the course of our research involving the Luche reduction
of 2-aryl-4-hydroxycyclopent-2-en-1-ones, we found that selective
deoxygenation takes place wherein protected/unprotected hydro-
xyl functionality is removed to afford the 2-aryl-cyclopent-2-en-
NaBH4, CeCl3, CH3OH
45-89%
OCH3
OCH3
R1O
R
R
: R= 3-Formyl-4-methoxyphenyl, R1= H
1a
1b
1c
2a
: R= 3-Hydroxymethyl-4-
methoxyphenyl
2b: R= 4-Methoxyphenyl
: R= 3-(1-Hydroxyethyl)-4-
methoxyphenyl
2d: R=H
1
: R= 4-Methoxyphenyl, R = H
: R= 3-Acetyl-4-methoxyphenyl, R1= H
2c
1d: R= 4-Methoxyphenyl, R1= TBDMS
1e: R=R1=H
1f: R=H, R1= TBDMS
OH
1. ClCOOEt, TEA, THF
OH
1g: R=H, R1= Ac
R
R1
R
1
1h
1i
R1
: R=H, R = Bz
2. CeCl3.7H2O, NaBH4,
EtOH
1
: R=H, R = TBDPS
O
Scheme 3. Selective, reductive deoxygenation of compounds 1.
Scheme 1. Deoxygenation of 2-acylphenols (Ref. 13).
1-ones and the results are reported herein. It is noteworthy that
deoxygenation of hydroxyl functionality under Luche reduction
conditions is not reported in the literature.
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetlet.2014.07.122
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

5242
S. R. Bavikar et al. / Tetrahedron Letters 55 (2014) 5241–5243
Table 1
Table 2
Selective reduction of compounds 1
Selective reduction of compounds 1j–1m
Entry Reactant
Product
Yielda (%)
Entry
Reactant
O
Product
Yielda (%)
78
O
O
O
O
O
O
O
1
2
O
O
HO
O
2 e
HO
1 j
1
2
3
45
O
O
HO
OHC
O
O
67
43
O
2 e
2 a
1 a
O
1 k
O
OH
O
O
O
O
O
NO2
NO2
O
O
3
4
HO
O
HO
O
HO
1l
2 f
89
O
OH
O
O
75
O
O
1 b
2 b
1 m
2 g
O
O
O
O
O
a
Isolated yield; variable amount of starting material was recovered.
O
O
HO
Based on the reported information,2 the substituted cyclopente-
O
55
none alcohol 1a was subjected to Luche reduction with an aim to
obtain the corresponding diol. There was no reaction with one
equivalent of sodium borohydride and cerium chloride so the reac-
tion was attempted with varying amounts of sodium borohydride
and cerium chloride. To our surprise, when the reaction was car-
ried out with 2 equiv of cerium chloride and 3 equiv of sodium
borohydride, the substituted cyclopentenone 2a was obtained in
45% yield (Scheme 2) and rest of the starting material was
recovered.
O
O
OH
2 c
O
1 c
O
O
O
O
O
O
O
O
Si
O
4
5
50
85
Thus, the ketone carbonyl in 1a survived while the hydroxyl
functionality was reductively removed and aldehyde was reduced
to alcohol to afford the substituted cyclopentenone 2a.
O
O
2 b
1 d
This unprecedented interesting result prompted us to check the
generality of the reaction and a number of cyclopentenone alcohols
were subjected to Luche reduction (Scheme 3).
O
O
O
O
O
O
HO
It was observed that in all the above cases,14,15 deoxygenation
of cyclopentenone alcohols 1 took place to give cyclopentenones
2 in 2–3 h, instead of the reduction of ketone functionality, in good
yields (Table 1).
O
O
O
O
2 d
1 e
O
O
O
O
O
6
7
55
51
The reaction was further studied for its scope and limitations.
When 4-hydroxy-2-phenylcyclopent-2-en-1-one (1j) was sub-
jected to similar reaction (Table 2, entry 1), 2-phenylcyclopent-2-
en-1-one (2e) was obtained in 78% yield while the reaction of 4-
acetoxy-2-phenylcyclopent-2-en-1-one (1k) afforded 2-phenylcy-
clopent-2-en-1-one (2e) in 67% yield (Table 2, entry 2). The reac-
tion of 4-hydroxy-2-(4-nitrophenyl)cyclopent-2-en-1-one (1l)
was slow and incomplete and resulted in the formation of 1,4-
dihydroxy-2-(4-nitrophenyl)cyclopent-2-ene (2f) in 43% yield
after 4 h. The corresponding 4-dehydroxylated product 2-(4-nitro-
phenyl) cyclopent-2-en-1-one was not obtained. Similarly, 4-acet-
Si
O
O
O
2 d
1 f
O
O
O
O
O
O
O
O
O
O
O
O
2 d
2 d
1 g
O
O
O
O
O
8
65
O
O
O
oxycyclopent-2-en-1-one
(1m)
provided
1-acetoxy-4-
1 h
hydroxycyclopent-2-ene (2g) in 75% yield and cyclopent-2-en-1-
one was not obtained.
O
O
O
Thus, it was observed that the 4-(un)protectedhydroxycyclo-
pent-2-en-1-ones bearing phenyl ring with electron donating sub-
stituent or unsubstituted phenyl ring, at 2-position of
cyclopentenone undergo deoxygenation at 4-position while 4-
(un)protectedhydroxycyclopent-2-en-1-ones bearing phenyl ring,
with electron withdrawing substituent (e.g., nitro group), at 2-
position of cyclopentenone undergo usual reduction of ketone
functionality. In case of substrates with same substituents on aro-
O
O
Si
9
49
O
O
O
2 d
1i
Isolated yield; variable amount of starting material was recovered.
a

S. R. Bavikar et al. / Tetrahedron Letters 55 (2014) 5241–5243
5243
CeCl2
CeCl2
O
O
O
CeCl3
NaBH4
R
R
R
R1O
R1
R1
O
O
1
3
CeCl3
4
CeCl3
R=H or electron donating substituent
CeCl2
O
CeCl2
O
O
MeOH
H
B
H
H
H
R
R
R
Na
2
6
5
Scheme 4. Proposed mechanism for deoxygenation.
3. Gemal, A. L.; Luche, J. L. J. Am. Chem. Soc. 1981, 103, 5454–5459.
4. Crimmins, M. T.; Gould, L. D. J. Am. Chem. Soc. 1987, 109, 6199–6200.
5. Parker, K. A.; Fokas, D. J. Am. Chem. Soc. 1992, 114, 9688–9689.
6. Sato, K.; Bokura, M.; Moriyama, H.; Igarashi, T. Chem. Lett. 1994, 23, 37–40.
7. Nishikawa, T.; Asai, M.; Ohyabu, N.; Yamamoto, N.; Isobe, M. Angew. Chem., Int.
Ed. 1999, 38, 3081–3084.
8. Winkler, J. D.; Rouse, M. B.; Greaney, M. F.; Harriison, S. J.; Jeon, Y. T. J. Am.
Chem. Soc. 2002, 124, 9726–9728.
9. Veitch, G. E.; Beckmann, E.; Burke, B. J.; Boyer, A. J.; Ayats, C.; Ley, S. V. Angew.
Chem., Int. Ed. 2007, 46, 7633–7635.
matic ring, the substrates with 4-hydroxy groups give better yields
than the substrates with 4-protected hydroxyl groups (e.g., 1b gave
89% yield while 1d gave 50% yield. Also, 1e gave 85% yield while 1f,
1g, 1h, and 1i gave 55, 51, 65, and 49% yields respectively. Simi-
larly, 1j gave 78% yield whereas 1k afforded 67% yield). 4-(un)Pro-
tectedhydroxycyclopent-2-en-1-ones (e.g., 1m) without phenyl
ring undergo normal reduction of ketone.
The proposed mechanism for this reaction is shown in
Scheme 4.
10. Liu, L. Z.; Han, J. C.; Yue, G. Z.; Li, C. C.; Yang, Z. J. Am. Chem. Soc. 2010, 132,
13608–13609.
In conclusion, the present manuscript reports interesting preli-
minary results about an unprecedented method for the selective
one-step deoxygenation of 2-aryl-4-hydroxycyclopent-2-en-1-
ones to afford 2-aryl-cyclopent-2-en-1-ones. The electron donating
substituents on phenyl ring favor the deoxygenation while the
electron withdrawing substituents favor the normal reduction of
ketone to give corresponding hydroxy compounds.
11. Hannessian, S.; Vakiti, R. R.; Dorich, S.; Banerjee, S.; Lacomte, F.; Delvalle, J. R.;
Zhang, J.; Simard, B. D. Angew. Chem., Int. Ed. 2011, 50, 3497–3500.
12. Fruhmann, P.; Hametner, C.; Mikula, H.; Adam, G.; Krska, R.; Frohlich, J. Toxins
2014, 6, 325–336.
13. Yuan, H.; Chen, H.; Jin, H.; Li, B.; Shen, Y.; Shan, L.; Sun, Q.; Zhang, W.
Tetrahedron Lett. 2013, 54, 2776–2780.
14. Spectral data for all products obtained are given in the Supplementary data.
15. Representative experimental procedure: Preparation of (3-(4-methoxyphenyl)-2-
(3,4,5-trimethoxyphenyl)cyclopent-2-en-1-one: Compound 1b (100 mg,
0.27 mmol) and CeCl3 (132 mg, 0.54 mmol) in MeOH (10 ml) were stirred in
a two-necked round bottom flask at 0 °C for 10 min. NaBH4 (30 mg, 0.81 mmol)
was added to it and the mixture was stirred and allowed to reach room
temperature. Reaction was monitored by TLC (60% ethyl acetate in pet ether
was used as a solvent system). After 2 h, water was added to it. Methanol in the
reaction mixture was removed by using rotavapor and the product was
extracted with ethyl acetate to obtain crude compound which was purified by
using column chromatography to obtain pure compound 2b (85 mg, 89%); 1H
NMR (400 MHz, CDCl3): d 2.67–2.72 (m, 2H), 3.03–3.08 (m, 2H), 3.75 (s, 6H),
3.82 (s, 3H), 3.87 (s, 3H), 6.44 (s, 2H), 6.82 (d, J = 8 Hz, 2H), 7.36 (d, J = 8 Hz,
2H); 13C NMR (100 MHz, CDCl3): d 29.07, 34.59, 55.31, 55.98 (2C), 60.83,
106.33 (2C), 113.74 (2C), 127.62, 128.43, 129.95 (2C), 137.50, 138.30, 153.43
(2C), 161.03, 167.27, 207.64; IR: 1698 cmÀ1; HRMS (ESI) m/z calculated for
[C21H22O5+H]: 355.1540, found: 355.1541; [C21H22O5+Na]: 377.1359, found:
377.1360.
Acknowledgements
We thank CSIR-India for financial support (Project no: CSC0108;
ORIGIN) and Dr. P. Rajmohanan for fruitful discussions.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.07.
122.
References and notes
1. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226–2227.
2. Gemal, A. L.; Luche, J. L. J. Org. Chem. 1979, 44, 4187–4189.